Decrease of rotenone inhibition is a sensitive parameter of complex I damage in brain non‐synaptic mitochondria of aged rats

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Abstract
We investigated NADH oxidation in non‐synaptic and synaptic mitochondria from brain cortex of 4‐ and 24‐month‐old rats. The NADH oxidase activity was significantly lower in non‐synaptic mitochondria from aged rats; we also found a significant decrease of sensitivity of NADH oxidation to the specific Complex I inhibitor, rotenone. Since the rotenone‐binding site encompasses Complex I subunits encoded by mtDNA, these results are in accordance with the mitochondrial theory of aging, whereby somatic mtDNA mutations are at the basis of cellular senescence. Accordingly, a 5 kb deletion was detected only in the cortex of the aged animals.